Process for the preparation of moxifloxacin hydrochloride

ABSTRACT

The present invention relates to an improved process for the preparation of Moxifloxacin hydrochloride from the ethyl 1-cyclopropyl 6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylate through a novel intermediate (4aS-Cis)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic acid-0 3 ,0 4 )bis(acyloxy-0) borate.

The present invention relates to a process for preparation ofMoxifloxacin hydrochloride, using a novel intermediate namely(4aS-Cis)-(1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylicacid-O³,O⁴)bis(acyloxy-O) borate.

BACKGROUND OF THE INVENTION

Moxifloxacin Hydrochloride namely(4aS-Cis)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid hydrochloride has the formula

Moxifloxacin is a fluoroquinolone broad spectrum antibacterialparticularly against Gram-positive bacteria significantly better thanthose of Sparfloxacin and Ciprofloxacin that was disclosed in EP No350,733 and EP No 550,903. Moxifloxacin has activity againstGram-negative and Gram-positive organisms, including Streptococcuspneumonia, Staphylococcus aureus, Pseudomonas aeruginosa, particularlyagainst the respiratory disease-causing pathogens like Mycoplasmapneumonia, Mycobacterium tuberculosis, Chlamydia pneumoniae and theactivity shown to be unaffected by B-lactamases.

U.S. Pat. No 5,157,117 discloses(1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O) borate and a process for itspreparation by reactingethyl-1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylate with Boric acid and acetic anhydride in presence of zincchloride and its conversion to Gatifloxacin hydrochloride.

Hydrates of Moxifloxacin hydrochloride known are the anhydrous andmonohydrate. U.S. Pat. No. 5,849,752 discloses the monohydrate ofMoxifloxacin hydrochloride and its preparation by treating the anhydrouscrystalline form with ethanol/water mixtures.

The prior art disclosed in European Patent No's EP 350,733, EP 550,903and EP 657,448 discloses the preparation of Moxifloxacin hydrochlorideinvolving the condensation of1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid or its esters with (S,S) 2,8-Diaza bicyclo[4.3.0]nonanein presence of a base and its conversion to hydrochloride at highertemperatures leading to the desired Moxifloxacin along with itspositional isomer namely(4aS-Cis)-1-cyclopropyl-6-(2,8-diazabicyclo[4.3.0]non-8-yl)-7-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid as a major impurity. As the impurity and theMoxifloxacin are positional isomers they are difficult to separate.Purification of Moxifloxacin to remove this isomer results in loweryields thereby increasing the product cost. Similarly methods describedin the prior art involves the preparation of Moxifloxacin and then itsconversion to its hydrochloride thereby incorporating an additional stepin the manufacturing process also leading to lowering of yields.

It is a long felt need of the industry to provide high yielding and costeffective processes for the preparation of Moxifloxacin hydrochloride.

SUMMARY OF THE INVENTION

The main object of the present invention is to provide a high yieldingand cost effective process for the preparation of Moxifloxacinhydrochloride.

Another object of the invention is to provide a process for thepreparation of Moxifloxacin hydrochloride without the additional step ofisolation of Moxifloxacin.

Another object of the invention is to explore other hydrates ofMoxifloxacin hydrochloride.

Another object of the invention is to provide the fingerprinting ofMoxifloxacin hydrochloride pseudohydrate prepared by the inventedprocess.

Another object of the invention is to provide a process for theconversion of Moxifloxacin hydrochloride pseudohydrate to Moxifloxacinhydrochloride monohydrate.

Another object of the invention is to provide a process for thepreparation of the novel intermediate(4aS-Cis)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O)borate and its use in thepreparation for Moxifloxacin hydrochloride.

Another object of the invention is to provide fingerprinting of thenovel intermediate(4aS-Cis)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O)borate using NMR, IR and x-raydiffraction analysis.

Another object of the invention is to provide a process for thepreparation of(1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O)borate without using the catalystand its use for the preparation of Moxifloxacin hydrochloride.

Accordingly, the present invention relates to a method for thepreparation of Moxifloxacin hydrochloride from the ethyl1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylatethrough novel intermediate(4aS-Cis)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O)borate. The reaction ofethyl1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylate with boric acid and acetic anhydride without using anycatalystgives(1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O)borate which on condensation inpresence of a base(s) with (S,S)-2,8-Diazabicyclo[4.3.0]nonane inorganic polar solvent results the novel intermediate(4aS-Cis)-1-Cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O) borate. This intermediate isreacted with hydrochloric acid in presence of solvent to giveMoxifloxacin hydrochloride pseudo hydrate. The Moxifloxacinhydrochloride pseudohydrate is converted into Moxifloxacin hydrochloridemonohydrate by treating with hydrochloric acid in presence of ethanol.

The reaction scheme is given below:

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1: X-ray diffraction pattern of the(4aS-Cis)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O) borate.

FIG. 2: FTIR spectrum of the(4aS-Cis)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O)borate

FIG. 3: NMR spectrum of the(4aS-Cis)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O)borate

FIG. 4: FTIR spectrum of the Moxifloxacin hydrochloride psuedohydrate

FIG. 5: X-ray diffraction pattern of the Moxifloxacin hydrochloridepsuedohydrate

FIG. 6: FTIR spectrum of the Moxifloxacin hydrochloride anhydrous

FIG. 7: X-ray diffraction pattern of the Moxifloxacin hydrochlorideanhydrous

FIG. 8: FTIR spectrum of the Moxifloxacin hydrochloride monohydrate

FIG. 9: X-ray diffraction pattern of the Moxifloxacin hydrochloridemonohydrate

DETAILED DESCRIPTION OF THE INVENTION

The process of the present invention comprises steps as:

-   -   Reacting ethyl        1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline        carboxylate with a mixture of boric acid and acetic anhydride at        temperature above 50° C. without the use of catalyst    -   Separating        (1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline        carboxylic acid-O³,O⁴)bis(acyloxy-O) borate by cooling to low        temperature followed by dilution with water    -   Isolating and drying the        (1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline        carboxylic acid-O³,O⁴)bis(acyloxy-O)borate    -   Condensing        (1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline        carboxylic acid-O³,O⁴)bis(acyloxy-O)borate with        (S,S)-2,8-diazabicyclo[4.3.0]nonane in presence of base(s) in        organic polar solvent(s)    -   Optionally Isolating the novel intermediate after completion of        reaction        (4aS-Cis)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline        carboxylic acid-O³,O⁴)bis(acyloxy-O)borate    -   Optionally without isolating the intermediate, directly        proceeding to the preparation of Moxifloxacin hydrochloride by        reaction with hydrochloric acid in a solvent    -   Isolating and drying the Moxifloxacin hydrochloride        pseudohydrate    -   Optionally treating the Moxifloxacin hydrochloride pseudohydrate        with hydrochloric acid in ethanol to get Moxifloxacin        hydrochloride monohydrate

The prepared1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O)borate is a hydrate and the novelintermediate(4aS-Cis)-1-Cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O)borate is anhydrous, characterizedby chemical analysis NMR, IR spectrum and XRD.

Moxifloxacin hydrochloride pseudohydrate prepared by the process of thisinvention exhibits some novel characteristics such as water contentvarying from 0.5% to 1.0%, and high hygroscopic nature. However the XRDdata and IR patterns of the pseudohydrate as prepared remainssubstantially unaltered as illustrated in FIGS. 4 & 5.

The starting materials ethyl1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylate and [S,S]-2,8-diaza bicyclo[4.3.0]nonane are prepared byliterature reported methods.

Acetic anhydride is heated to about 70° C., and boric acid is added inlots. The reaction mass is stirred for about 1 hr to about 2 hrs attemperatures of about 70° C.-about 125° C., preferably at about 110° C.to-about 120° C., cooled to temperature of about 60° C.-about 100° C.,preferably to about 70° C. To this mixture,ethyl(1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylate is added, the temperature raised to about 90° C.-about 120°C., preferably to about 100° C. to about 110° C. and mixed for about 1hr to about 5 hrs preferably for about 1 hr. The reaction mass is cooledto temperature below 35° C., preferably to about 0° C.-about 20° C.,preferably to about 0° C. followed by addition of cold water and thenmixed for about 1 to about 4 hrs. The product formed is separated byconventional means, washed with water and dried to obtain1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O)borate.

(1-Cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O)borate is suspended in organic polarsolvents preferably DMSO, DMF, acetonitrile, ethanol and mixed with[S,S]-2,8-Diaza bicyclo[4.3.0]nonane in presence of organic, inorganicbase(s) preferably triethyl amine, DBU, diisopropylethyl amine,potassium carbonate at temperatures about 20° C.-about 120° C.,preferably at about 60° C.-about 80° C. for about 1 hr to about 6 hrs.After the completion of reaction the reaction mass is cooled. The novelintermediate(4aS-Cis)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O)borate is isolated by removal ofsolvent under vacuum below 60° C. preferably at about 40° C.-45° C.followed by addition of the hydrocarbons preferably hexane, heptane,cyclohexane, methyl cyclohexane, mixed for about 2 hrs, the product isfiltered and dried.

Alternatively it is possible to proceed to the preparation ofMoxifloxacin hydrochloride pseudohydrate without the isolation of theintermediate(4aS-Cis)-1-Cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O)borate as follows:

The reaction mass is diluted with short chain alcohol, with an optionalstep of the removal of insolubles (if any), adjusting the pH of thereaction mass to acidic with hydrochloric acid at temperatures below 35°C. preferably in the range of about 20° C. to about 25° C. and stirredfor about 2 to about 6 hrs. The alcohol is selected from C-1 to C-4alcohols preferably methanol and/or ethanol. The pH is adjusted to below2.0 preferably between below 0.5 and cooled to below 15° C. preferablybetween about 0° C. to about 5° C. and maintained for about 2 to about 6hrs. The product is separated and dried to obtain Moxifloxacinhydrochloride pseudohydrate.

In another embodiment of the invention, the isolated intermediate(4aS-Cis)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O) borate is converted directly toMoxifloxacin hydrochloride by dissolving in short chain alcoholpreferably ethanol, methanol, removing the insolubles if any, adjustingpH to below 2.0 preferably to below 0.5 with hydrochloric acid andmaintaining for about 1 hr to about 4 hrs preferably for about 2 hrs attemperatures in the range of about 20° C. to about 25° C. Aftercompletion of reaction, the reaction mass cooled to below 15° C.preferably in the range of about 0° C. to about 5° C. and maintained forabout 2 to about 6 hrs. The product is separated and dried to obtainMoxifloxacin hydrochloride pseudohydrate.

Moxifloxacin hydrochloride pseudohydrate upon mixing with hydrochloricacid in presence of ethanol at temperature yields Moxifloxacinhydrochloride monohydrate.

The invention is now illustrated with a few non-limiting examples.

EXAMPLE-I

Stage-1: Preparation of1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O)borate

Acetic anhydride (175 g) is heated to 70° C. and boric acid (30 g) isslowly added lot wise in a temperature range of 70° C. to 90° C. Thetemperature is then raised, maintained under reflux for 1 hr followed bycooling to about 70° C.Ethyl-1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylate (100 g) is added under stirring. The temperature is thenraised and maintained for 1 hr in the range of 100° C. to 105° C. Thereaction mass is cooled to 0° C., chilled water (400 ml) is added slowlyfollowed by cold water (600 ml) at temperature 0° C. to 5° C. andmaintained for 2 hrs at 0° C. to 5° C. The product which is a boronacetate complex is filtered, washed with water (500 ml) and dried at 55°C. to 60° C. under vacuum to constant weight.

The dry wt is 130.0 g corresponding to yield of 95.2%.

Stage-2: Preparation of(4aS-Cis)-1-Cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O)borate

The boron acetate complex (130 g) prepared in stage 1 is suspended inacetonitrile (650 ml), and [S,S]-2,8-diazabicyclo[4.3.0]nonane (47 g)and triethyl amine (72.9 g) are added. The temperature is raised toreflux and maintained for 1 hr. at reflux, followed by cooling to about40° C. The solvent is removed under vacuum at temperature below 40° C.,and n-hexane (200 ml) is added. After maintaining the reaction mass for1 hr at room temperature the product is isolated by filtration followedby washing of the wet cake with n-hexane. The product is dried at about45° C. to about 50° C. to constant weight.

Dry wt of the novel intermediate is 117.0 g corresponding to yield of71.5%.

Elemental analysis: C: 56.42%, H: 5.62%, N: 7.76% and the calculatedvalues for the intermediate, formula C₂₅H₂₉BFN₃O₈ C: 56.6%, H: 5.47%, N:7.92%

IR Spectrum (KBr, cm⁻¹): 3415, 3332, 2936, 1718, 1630, 1573, 1526, 1445,1273, 1042, 935, 860, 798, 682

¹H NMR (200 MHz, CDCl₃, ppm): 9.00 (1H), 7.82 (1H), 4.12 (4H), 3.57(3H), 3.43 (4H), 3.07 (2H), 2.75 (2H), 2.4 (1H), 2.1 (6H), 1.84 (2H),1.6 (1H), 1.31 (2H)

Mass Spectrum (M⁺): 530.3 [M⁺H], 470.2 [M⁺-CH₃COOH], 428.2[M⁺-(CH₃CO)₂O, 100%], 402.2, 388.2

Stage-3: Preparation of Moxifloxacin Hydrochloride Pseudohydrate

The intermediate (117 g) prepared stage-2 is dissolved in ethanol (600ml) by stirring for about 30 min. at room temperature and the insolublesif any are filtered off. pH of the filtrate is adjusted to about 0.5 byaddition of hydrochloric acid at room temperature and maintained for 2hrs. The reaction mass is cooled, and maintained for two hrs, at about0° C. to about 5° C. The product is filtered, washed with chilledethanol (50 ml) and dried at about 50° C. to about 55° C. till constantweight.

The dry weight of the Moxifloxacin hydrochloride pseudohydrate is 87.5 gcorresponding to yield of 91.0%. Water content of the product by KF is0.64% w/w.

X-ray diffraction pattern data are given in Table-1

EXAMPLE-II

Stage-2: Preparation of Moxifloxacin Pseudohydrate with out Isolating(4aS-Cis)-1-Cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylicacid-O³,O⁴)bis(acyloxy-O) borate

The boron acetate complex (130 g) prepared in stage-1 of Example-1 issuspended in acetonitrile (650 ml) and[S,S]-2,8-Diazabicyclo[4.3.0]nonane (47 g) & triethyl amine (72.9 g) areadded. Temperature of the reaction mass is raised to reflux, maintainedfor 1 hr. at reflux and cooled to room temperature. Methanol (600 ml) isadded and maintained for 30 min at room temperature to obtain a clearsolution. The solution is filtered to remove insolubles if any and pH ofthe filtrate is adjusted to about 0.5 with hydrochloric acid (57.5 g).The reaction mass is maintained for 2 hrs at temperature in the range ofabout 20° C. to about 25° C., cooled to 0° C. followed by maintainingthe reaction mass at about 0° C. to about 5° C. for 2 hrs. The productis filtered, washed with methanol (50 ml) and dried at about 50° C. to55° C. until constant weight.

Dry wt of the Moxifloxacin hydrochloride pseudohydrate is 88 gcorresponding to yield of 68.7%.

EXAMPLE-III: Preparation of Moxifloxacin Hydrochloride Monohydrate

Moxifloxacin hydrochloride (50 g) prepared as above is suspended in amixture of ethanol (250 ml) and hydrochloric acid (25 ml). Raised thetemperature, maintained for two hrs at 40° C. to 45° C. followed bycooling to about 25° C. The product is filtered and dried under vacuumat 50-55° C. until become constant weight.

Dry wt of Moxifloxacin hydrochloride monohydrate is 46 g correspondingto yield of 90.5%.

The IR spectral data and XRD pattern are identical with availableMoxifloxacin hydrochloride monohydrate. TABLE 1 S. No PSEUDOHYDRATE MONOHYDRATE ANHYDROUS FTIR PEAKS OF MOXIFLOXACIN HYDROCHLORIDE 1 3669 35303527 2 3357 3472 3469 3 2950 2925 2929 4 2894 2525 2524 5 2548 2456 61730 2427 2427 7 1708 1709 1709 8 1623 1623 1621 9 1515 1516 1512 101456 1456 1452 11 1373 1395 12 1354 1372 1371 13 1326 1353 1353 14 11831185 1186 15 1046 1046 1048 16 1028 994 994 17 938 938 938 18 875 875709 19 835 835 834 20 804 804 804 21 722 722 722 XRD PEAKS OFMOXIFLOXACIN HYDROCHLORIDE 1 5.8 5.7 5.8 2 7.2 8.3 8.6 3 8.6 10 10.2 410.4 11.4 11.5 5 12.4 13.3 13.5 6 13.3 14.3 14.3 7 14.6 15.5 15 8 14.916.9 15.7 9 15.2 17.3 17.2 10 16.7 17.8 17.4 11 17.3 18.4 18.2 12 17.919.5 18.8 13 18.7 20.2 19.2 14 19.8 23.5 19.5 15 21.7 24 20.6 16 22.426.4 17 24.7 26.6 21.5 18 25.2 27.3 22.5 19 25.8 29 20 26.6 31.3 21 2735 22 27.4 36.6 23 27.9 38.6 24 28.4 39.2 25 29 43.2 26 30 27 31.6 2832.3 29 35 30 37.6 31 39.1 32 41.3 33 41.9 34 43.9

1. A process for the preparation of Moxifloxacin hydrochloridemonohydrate comprising steps Treating(4aS-Cis)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid (-O³,O⁴)bis(acyloxy-O) borate with hydrochloric acid ina solvent Isolating and drying the Moxifloxacin hydrochloride Treatingthe Moxifloxacin hydrochloride with hydrochloric acid in ethanol to getMoxifloxacin hydrochloride monohydrate
 2. A process as claimed inclaim-1, wherein hydrochloric acid is gaseous or aqueous or dissolved ina solvent
 3. A process as claimed in claim-1, wherein the solvent usedis a short chain alkanol
 4. A process as claimed in claim-3, wherein theshort chain alkanol is preferably methanol, ethanol and isopropanol 5.Moxifloxacin hydrochloride which is characterized by an infraredabsorption comprising bands at 3669, 3357, 2950, 2894, 2548, 1730, 1708,1623, 1515, 1456, 1373, 1354, 1326, 1183, 1046, 1028, 938, 875, 835, 804and 722 cm⁻¹
 6. Moxifloxacin hydrochloride which is characterized by apowder X-ray diffraction pattern comprising peaks at about 5.8, 7.2,8.6, 10.4, 12.4, 13.3, 14.6, 14.9, 15.2, 16.7, 17.3, 17.9, 18.7, 19.8,21.7, 22.4, 24.7, 25.2, 25.8, 26.6, 27.0, 27.4, 27.9, 28.4, 29.0, 30.0,31.6, 32.3, 35.0, 37.6, 39.1, 41.3, 41.9 and 43.9±0.2 degrees two-theta.7. Crystalline(4aS-Cis)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O)borate
 8. As claimed in claim-8 thenovel intermediate which is characterized by an infrared absorptioncomprising bands at 3415, 3332, 2936, 1718, 1630, 1573, 1526, 1445,1273, 1042, 935, 860, 798, 682 cm⁻¹
 9. A process for the preparation ofa novel intermediate(4aS-Cis)-1-Cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis (acyloxy-O)borate comprising: Reacting ethyl1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylate with a mixture of boric acid and acetic anhydride attemperature above 50° C. without the use of catalyst Precipitating(1-Cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O)borate by cooling to low temperaturefollowed by diluting with water Isolating and drying the(1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O)borate Condensing(1-Cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O)borate with(S,S)-2,8-Diazabicyclo[4.3.0]nonane in presence of base(s) in organicpolar solvent(s) Crystallizing(4aS-Cis)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O)borate Isolating and drying of(4aS-Cis)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O)borate
 10. The process as claimed inclaim 9, wherein the temperature for the reaction of ethyl1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylate with the mixture of boric acid and acetic anhydride is inthe range of 90° C. to 120° C.
 11. The process as claimed in claim 9,wherein the organic polar solvents is selected from acetonitrile or DMSOor DMF.
 12. The process as claimed in claims 9, wherein the base(s) usedis organic or inorganic base
 13. The process as claimed in claims 12,wherein the organic base is selected from triethylamine or diisopropylethylamine or DBU
 14. The process as claimed in claims 12, wherein theinorganic base is potassium carbonate
 15. The process as claimed inclaim 9, wherein the temperature for the condensation reaction is in therange of 30° C. to 100° C., preferably from 60° C. to 80° C.
 16. Theprocess as claimed in claim 9, wherein the crystallization of(4aS-Cis)-1-Cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O³,O⁴)bis(acyloxy-O)borate is carried out by removal ofsolvent and adding a second solvent
 17. The process as claimed in claim16, wherein the second solvent is selected from hydrocarbons of C-5 toC-7
 18. The process as claimed in claim 17, wherein the hydrocarbon isalkanes, cycloalkanes or mixtures thereof
 19. The process as claimed inclaim 17, wherein the hydrocarbon is n-hexane, n-heptane, cyclohexane,methyl cyclohexane or mixtures thereof.